Opinion articles

Friday, May 4, 2012

ASH's Hematology Research Agenda: More Bang for the Federal Buck



Chair, Department of Medicine, University of Florida and Shands Hospital; 

Chair,  Committee on Scientific Affairs, American Society of Hematology


At a time when Washington is discussing not whether to cut the National Institute of Health’s budget but rather by how much, the American Society of Hematology is urging the scientific community, funding agencies, Congress, and the American public to remember the enormous returns biomedical research has yielded from modest NIH investments over the past decade.

In its recently released ASH Agenda for Hematology Research, the Society emphasizes the enormous progress the field has made over the past 10 years: Chronic myeloid leukemia (CML) has become a manageable disease that is easily treated, the vast majority of cases of acute promyelocytic leukemia (APL) has become curable, and the survival rate for myeloma has nearly doubled.


The foundation of each of these advances has been NIH funding. NIH sponsored the early work on the ABL kinase inhibitors in CML, the role of retinoic acid in APL, and the activities of both the proteosome inhibitors and immunomodulatory drugs in myeloma.


If accountability is the new paradigm in the federal government, then ASH presents a cogent argument that the biggest bang for the government’s buck is in NIH-funded research. The lives saved and the suffering relieved by these discoveries are immeasurable. However, there is another important argument for maintaining NIH funding: Biopharmaceuticals are one of the few remaining U.S. strongholds in global trade. Other nations look with envy at our drug discovery enterprise, and some, such as China, are pouring enormous resources into their own efforts that will soon surpass ours.


The NIH budget needs to be seen as an important economic driver that creates jobs. In addition to putting Americans to work and keeping them there, jobs created by new biomedical research projects provide several crucial downstream benefits. More jobs translate to more patients with access to health insurance and less anguish over obtaining care for the uninsured. More jobs improve the economy for everyone. It is no surprise that the dry pipeline of new potential cancer therapy drugs coincides with the significantly decreased funding rates of individual investigator grants. Most current cancer therapeutics on track for FDA approval are not innovative, first-in-class drugs, but rather derivatives of other agents. At the heart of this problem are systematic decreases in funding to support basic research that will define these new targets.  


As Relevant for the Community Hematologist/Oncologist as for the Academician

If we want to maintain the rate of drug discovery and development that will create new industries and new jobs, we need to maintain -- and increase -- federal funding for the NIH. From this viewpoint, this is as relevant for the community hematologist/oncologist as for the academician, since all are interested in robust new therapies for patients with devastating illnesses. It is clear to everyone that the status quo is not acceptable.


If NIH funding is to be maintained, what should the research agenda be to ensure that the rate of advance is sustained? ASH convened a group of senior hematology investigators from around the world to determine the major unsolved problems currently facing the field. This group identified seven critical problems that need to be addressed in the next three years in order for the field to advance. These high-need areas, outlined in ASH’s Research Agenda, include induced pluripotent stem (iPS) cells and regenerative medicine, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in the elderly, hematopoietic stem cell transplantation and management of graft-versus-host disease (GVHD), sickle cell disease, deep-vein thrombosis (DVT) and venous thromboembolism (VTE), and childhood leukemia. The ASH Research Agenda also discusses the importance of harnessing recent discoveries of important genetic and biologic markers to personalize and improve treatments for our patients.


Induced Pluripotent Cells

Of our outlined priority areas, perhaps the most exciting is that of iPS cells, which make it possible for any patient’s skin or bone marrow cells to be re-programmed into stem cells. These cells can then be differentiated into different tissues, opening the way for regeneration medicine. Diseased or even malignant organs can be potentially replaced, but serious problems remain. These iPS cells grow slower, are more difficult to differentiate, and are more genetically unstable than normal stem cells. Finding answers to these problems could open up the possibility of inexpensive transplantation sources, whereby the patient’s own cells serve as the donor organ.


MDS/AML in Elderly

Another area commanding attention is MDS and AML in the elderly. Since myelodysplasia was until recently not a reportable cancer, its true incidence remains unknown. However, as physicians become more aware of it, it has been found to be increasingly common, especially in the elderly. This is a problem in our aging population, because this disease is much more aggressive in the elderly, and elderly patients respond poorly to current therapies. MDS often culminates in AML, which is also far less treatable in the elderly.         



A third priority area is improving the success rates of hematopoietic stem cell transplants by improving the management of GVHD. While the number of allogeneic stem cell transplants continues to increase worldwide, GVHD remains the major limiting factor to its success. The mechanism by which the donor’s immune system recognizes a given host as foreign and mediates epithelial tissue destruction is not known. Research efforts to identify new targets for therapy are desperately needed. If new therapies for GVHD could be defined, that would markedly increase the number and type of transplants currently available.


Thromboembolic Disease

Finally, thromboembolic disease has become an epidemic in the U.S., perhaps from increased obesity and sedentary lifestyles. DVT occurs in more than 200,000 Americans each year, and disproportionately strikes cancer patients. Although treatment advances for this disease in the form of small-molecular-weight heparins and direct thrombin inhibitors have been made, preventing and managing disease  remains complex and additional research is still of critical importance.


Benefited Other Medical Disciplines

The ASH Research Agenda also outlines how advances in hematology have benefited many other medical disciplines. The advent of imatinib for CML opened up the possibility of kinase inhibition for many other cancers. But broader than oncology, basic and clinical research in the field of hematology has enhanced care of stroke, improved care of myocardial infarction, and improved surgical outcomes by decreasing postoperative thromboembolic disease. ASH presents a compelling rationale for federal support of hematology research because discoveries in this field can advance so many other medical specialties.


Call to Action

We all face an enormous challenge in maintaining NIH research funding, but we must not remain silent. ASH’s Research Agenda is meant to be a call to action for the biomedical research community to challenge the misguided notion that reducing federal research dollars will save the nation money. We need to insist that the questions in this hematology Research Agenda be addressed, and this requires NIH funding.


Our best advocates are our patients and their families, and enlisting them to promote biomedical research funding is perhaps the best tool to make this happen. This ASH Research Agenda gives them specific guidance to direct their and our efforts. 


To download a copy of the ASH Agenda for Hematology Research, visit http://www.hematology.org/researchagenda